The present invention relates to glycolic acid or a pharmaceutically acceptable salt or ester thereof, and/or D-lactic acid or a pharmaceutically acceptable Salt or ester thereof for use in the treatment of a neurodegenerative disease which is associated with a decline in mitochondrial activity. The present invention also relates to a pharmaceutical formulation comprising glycolic acid or a pharmaceutically acceptable salt or ester thereof in an amount of at least 0.005% (w/w), preferably at least 0.0075% (w/w) and most preferably at least 0.01% (w/w), and/or D-lactic acid or a pharmaceutically acceptable salt or ester thereof in an amount of at least 1.5% (w/w), preferably at least 3% (w/w) and most preferably at least 4.5% (w/w).
In this specification, a number of documents including patent applications and manufacturer's manuals are cited. The disclosure of these documents, while not considered relevant for the patentability of this invention, is herewith incorporated by reference in its entirety. More specifically, all referenced documents are incorporated by reference to the same extent as if each individual document was specifically and individually indicated to be incorporated by reference.
The term “neurodegenerative diseases” Is an umbrella term for diseases being associated with progressive loss of structure or function of neurons, including cell death of neurons. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death (in particular apoptosis). Neurodegenerative diseases affect many body activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical condition such as alcoholism, a tumor, or a stroke. Other causes may include toxins, chemicals, and viruses. The cause of some is, however, still not known.
One example of a neurodegenerative disease is Parkinson's disease. Parkinson's disease is caused by inexorable deterioration of dopaminergic neurons from the substantia nigra. Although little is known about the onset of Parkinson's disease, one clue is that a number of genes associated with the onset of Parkinson's disease are linked with mitochondrial activity (Corti et al., 2011). There is strong evidence that mitochondrial dysfunction and oxidative stress play a causal role in Parkinson's disease and in neurodegenerative disease pathogenesis in general. Other neurodegenerative diseases in which mitochondrial dysfunction and oxidative stress were observed include but are not limited to Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS) (Lin and Beal (2006), Nature 443, 787-795).
Neurodegenerative diseases are among the most serious health problems facing modern society. Many of these disorders become more common with advancing age, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and many others. The burden of these neurodegenerative diseases is growing inexorably as the population ages, with enormous economic and human costs. For example, Alzheimer's Disease International (ADI) estimates in its 2010 report that there are 35.6 million people with AD worldwide as of 2010, and that this will grow to 115.4 million people by 2050. In industrialized countries the prevalence of Parkinson's disease is about 1% for people over 60, with estimates of up to 4% for people in the highest age groups (Lau and Breteler (2006), Lancet Neurol.; 5(6):525-35).
To date a combination of vitamins, optimize patients' nutrition and general health, and prevent worsening of symptoms during times of illness and physiologic stress is used to treat neurodegenerative diseases (see Parikh et al (2009), Current Treatment Options in Neurology, 11:414-430 for review). However, most neurodegenerative diseases have no cure or a can only be insufficiently cured. Hence, there is an ongoing need of novel treatment possibilities that may help improving symptoms, relieve pain, and increase mobility in patients suffering from a neurodegenerative disease.